A junctional protein (red) clumps (arrows) at lymph vessel entryways but is continuous (arrowheads) in the lower collecting ducts.

A study by Baluk et al. (page 2349) reveals how the organization of junctional proteins might keep endothelial cells in lymphatic vessels buttoned up but still allow fluid and cells to enter.

Lymph flows through a network that starts out as tiny vessels and then widens into collecting ducts. But how lymph gets from the blood into lymph vessels through the endothelial barrier is unclear. One model suggests that endothelial cells lack junctions and thus glide apart under mechanical stress. Another proposes that junctions break down to permit fluid entry and then reseal.

Baluk et al. did not favor either idea, as junctions are required to maintain vessel structure, and their breakdown and reconstruction spell excessive wear and tear on the vessel. The team traced the expression of junctional proteins in lymphatic vessels in mouse airways and found that the proteins formed continuous zipper-like structures in collecting ducts. In the tiny vessel entryways, however, they were organized into button-like clumps at the corners of adjacent endothelial cells.

The flaps between the buttons probably allow fluid to enter, but the authors are not sure whether cells also crawl in through these openings. In the lymph networks of mice whose airways were inflamed, leukocytes sidled alongside the buttoned openings rather than the zippered ends. But the team is yet to catch cells in the act of creeping through.